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Modulation of the combinatorial code of odorant receptor response patterns in odorant mixtures.
Molecular and Cellular Neuroscience ( IF 2.6 ) Pub Date : 2020-02-12 , DOI: 10.1016/j.mcn.2020.103469
Claire A de March 1 , William B Titlow 2 , Tomoko Sengoku 2 , Patrick Breheny 3 , Hiroaki Matsunami 4 , Timothy S McClintock 2
Affiliation  

The perception of odors relies on combinatorial codes consisting of odorant receptor (OR) response patterns to encode odor identity. Modulation of these patterns by odorant interactions at ORs potentially explains several olfactory phenomena: mixture suppression, unpredictable sensory outcomes, and the perception of odorant mixtures as unique objects. We determined OR response patterns to 4 odorants and 3 binary mixtures in vivo in mice, identifying 30 responsive ORs. These patterns typically had a few strongly responsive ORs and a greater number of weakly responsive ORs. ORs responsive to an odorant were often unrelated sequences distributed across several OR subfamilies. Mixture responses predicted pharmacological interactions between odorants, which were tested in vitro by heterologous expression of ORs in cultured cells, providing independent evidence confirming odorant agonists for 13 ORs and identifying both suppressive and additive effects. This included 11 instances of antagonism of ORs by an odorant, 1 instance of additive responses to a binary mixture, 1 instance of suppression of a strong agonist by a weak agonist, and the discovery of an inverse agonist for an OR. Interactions between odorants at ORs are common even when the odorants are not known to interact perceptually in humans, and in some cases interactions at mouse ORs correlate with the ability of humans to perceive an odorant in a mixture.

中文翻译:

气味混合物中气味受体响应模式的组合代码的调制。

气味的感知依赖于由气味受体(OR)响应模式组成的组合代码来编码气味身份。通过OR处的气味剂相互作用对这些模式的调节可能解释了几种嗅觉现象:混合物抑制,不可预测的感官结果以及将气味混合物视为独特的对象。我们确定了对小鼠体内4种气味和3种二元混合物的OR反应模式,确定了30种反应OR。这些模式通常具有一些强响应的OR和大量弱响应的OR。对气味剂有反应的OR通常是不相关的序列,分布在多个OR子家族中。混合物反应可预测加味剂之间的药理相互作用,这是通过体外培养的细胞中异源表达来体外测试的,提供独立的证据来确认13种OR的增味剂激动剂,并确定抑制作用和累加作用。这包括11种实例对气味剂的OR拮抗作用,1种实例对二元混合物的加成反应,1种实例的弱激动剂抑制强激动剂和发现OR反向激动剂的情况。即使不知道人类中的增香剂之间在气味上的相互作用也是很常见的,并且在某些情况下,小鼠OR处的相互作用与人类感知混合物中增香剂的能力相关。1个实例是弱激动剂抑制了强激动剂,并发现了OR反向激动剂。即使不知道人类中的增香剂之间在气味上的相互作用也是很常见的,并且在某些情况下,小鼠OR处的相互作用与人类感知混合物中增香剂的能力相关。1个实例是弱激动剂抑制了强激动剂,并发现了OR反向激动剂。即使不知道人类中的增香剂之间在气味上的相互作用也是很常见的,并且在某些情况下,小鼠OR处的相互作用与人类感知混合物中增香剂的能力相关。
更新日期:2020-02-12
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